@article {13533, title = {Memory and language cognitive data harmonization across the United States and Mexico.}, journal = {Alzheimer{\textquoteright}s \& Dementia (Amsterdam, Netherlands)}, volume = {15}, year = {2023}, pages = {e12478}, abstract = {

INTRODUCTION: We used cultural neuropsychology-informed procedures to derive and validate harmonized scores representing memory and language across population-based studies in the United States and Mexico.

METHODS: Data were from the Health and Retirement Study Harmonized Cognitive Assessment Protocol (HRS-HCAP) and the Mexican Health and Aging Study (MHAS) Ancillary Study on Cognitive Aging (Mex-Cog). We statistically co-calibrated memory and language domains and performed differential item functioning (DIF) analysis using a cultural neuropsychological approach. We examined relationships among harmonized scores, age, and education.

RESULTS: We included 3170 participants from the HRS-HCAP (age~=~76.6 [standard deviation (SD): 7.5], 60\% female) and 2042 participants from the Mex-Cog (age~=~68.1 [SD: 9.0], 59\% female). Five of seven memory items and one of twelve language items demonstrated DIF by study. Harmonized memory and language scores showed expected associations with age and education.

DISCUSSION: A cultural neuropsychological approach to harmonization facilitates the generation of harmonized measures of memory and language function in cross-national studies.

HIGHLIGHTS: We harmonized memory and language scores across studies in the United States and Mexico.A cultural neuropsychological approach to data harmonization was used.Harmonized scores showed minimal measurement differences between cohorts.Future work can use these harmonized scores for cross-national studies of Alzheimer{\textquoteright}s disease and related dementias.

}, keywords = {Alzheimer{\textquoteright}s disease, cognitive aging, cross-cultural, cultural neuropsychology, harmonization}, issn = {2352-8729}, doi = {10.1002/dad2.12478}, author = {Arce Renter{\'\i}a, Miguel and Brice{\~n}o, Emily M and Chen, Diefei and Saenz, Joseph and Lindsay C Kobayashi and Gonzalez, Christopher and Vonk, Jet M J and Richard N Jones and Jennifer J Manly and Wong, Rebeca and David R Weir and Kenneth M. Langa and Gross, Alden L} } @article {13331, title = {The mode effect of web-based surveying on the 2018 HRS measure of cognitive functioning.}, journal = {J Gerontol B Psychol Sci Soc Sci}, year = {2023}, abstract = {

OBJECTIVES: Measuring cognition in an aging population is a public health priority. A move towards survey measurement via the web (as opposed to phone or in-person) is cost effective but challenging as it may induce bias in cognitive measures. We examine this possibility using an experiment embedded in the 2018 wave of data collection for the US Health and Retirement Study (HRS).

METHODS: We utilize techniques from multiple group item response theory to assess the effect of survey mode on performance on the HRS cognitive measure. We also study the problem of attrition by attempting to predict dropout and via approaches meant to minimize bias in subsequent inferences due to attrition.

RESULTS: We find evidence of an increase in scores for HRS respondents who are randomly assigned to the web-based mode of data collection in 2018. Web-based respondents score higher in 2018 than do phone-based respondents, and they show much larger gains relative to 2016 performance and subsequently larger declines in 2020. The bias in favor of web-based responding is observed across all items, but most pronounced for the serial 7 task and numeracy items. Due to the relative ease of the web-based mode, we suggest a cutscore of 12 being used to indicate CIND (cognitively impaired but not demented) status when using the web-based version rather than 11.

DISCUSSION: The difference in mode may be non-ignorable for many uses of the HRS cognitive measure. In particular, it may require reconsideration of some cutscore-based approaches to identify impairment.

}, issn = {1758-5368}, doi = {10.1093/geronb/gbad068}, author = {Domingue, Benjamin W and McCammon, Ryan and Brady T. West and Kenneth M. Langa and David R Weir and Jessica Faul} } @article {12989, title = {MODE EFFECTS ON COGNITIVE FUNCTIONING ASSESSMENTS IN THE HEALTH AND RETIREMENT STUDY}, journal = {Innovation in Aging}, volume = {6}, year = {2022}, pages = {163}, abstract = {As the population of the US ages, there is interest in assessing health conditions associated with age and longevity, such as age-related decline in cognitive functioning. As a result, there is an increased focus on measuring cognitive functioning in surveys of older populations. One challenge relates to conducting comparable measurement across survey modes (e.g., phone vs. web). Compounding this is that mode of survey administration is often not assigned randomly making inter-group comparison more difficult. This paper addresses these issues using a novel experiment embedded within the Health and Retirement Study (HRS). The HRS, a US-based cohort of people over 50, has measured cognition since its inception using both in-person and telephone modes. In 2018, a sample of approximately 3700 respondents was identified as web-eligible based on a prior report of internet access along with other selection criteria. Of these, 60\% were randomly selected for the web sample with the remainder serving as controls, assigned to telephone mode for comparison purposes. We deploy techniques from item response theory (IRT) and differential item functioning (DIF) to estimate the difference in cognitive functioning between web and phone respondents in 2018 based on longitudinal cognition data collected prior to 2018. Second, we estimate the overall effect of taking the survey via the web as compared to the phone. Third, we examine item-level variation in the magnitude of the mode effect and suggest possible methods for adjustment to support longitudinal consistency. These results are important in guiding future research that utilizes web-based cognitive measures.}, keywords = {Cognition, cognitive functioning assessments}, doi = {10.1093/geroni/igac059.652}, author = {Jessica Faul and Domingue, Ben and Stenhaug, Ben and Brady T. West and Kenneth M. Langa and David R Weir} } @article {12126, title = {Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits.}, journal = {Human Genetics and Genomics Advances}, volume = {2}, year = {2021}, pages = {100013}, abstract = {

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (), synaptic function and neurotransmission (), as well as genes previously implicated in neuropsychiatric or stress-related disorders (). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.

}, keywords = {blood pressure traits}, issn = {2666-2477}, doi = {10.1016/j.xhgg.2020.100013}, author = {Sun, Daokun and Melissa Richard and Musani, Solomon K and Yun Ju Sung and Thomas W Winkler and Schwander, Karen and Jin-Fang Chai and Guo, Xiuqing and Kilpel{\"a}inen, Tuomas O and Vojinovic, Dina and Aschard, Hugues and Traci M Bartz and Bielak, Lawrence F and Brown, Michael R and Chitrala, Kumaraswamy and Hartwig, Fernando P and Horimoto, Andrea R V R and Liu, Yongmei and Alisa Manning and Noordam, Raymond and Smith, Albert V and Sarah E Harris and K{\"u}hnel, Brigitte and Lyytik{\"a}inen, Leo-Pekka and Ilja M Nolte and Rauramaa, Rainer and van der Most, Peter J and Wang, Rujia and Erin B Ware and Weiss, Stefan and Wen, Wanqing and Yanek, Lisa R and Dan E Arking and Donna K Arnett and Barac, Ana and Boerwinkle, Eric and Broeckel, Ulrich and Chakravarti, Aravinda and Chen, Yii-Der Ida and Cupples, L Adrienne and Davigulus, Martha L and de Las Fuentes, Lisa and de Mutsert, Ren{\'e}e and de Vries, Paul S and Delaney, Joseph A C and Ana V Diez Roux and D{\"o}rr, Marcus and Jessica Faul and Fretts, Amanda M and Gallo, Linda C and Hans-J{\"o}rgen Grabe and Gu, C Charles and Tamara B Harris and Hartman, Catharina C A and Heikkinen, Sami and Ikram, M Arfan and Isasi, Carmen and Johnson, W Craig and Jost Bruno Jonas and Kaplan, Robert C and Komulainen, Pirjo and Krieger, Jose E and Levy, Daniel and Liu, Jianjun and Kurt Lohman and Luik, Annemarie I and Martin, Lisa W and Meitinger, Thomas and Milaneschi, Yuri and Jeff O{\textquoteright}Connell and Walter R Palmas and Peters, Annette and Peyser, Patricia A and Pulkki-Raback, Laura and Raffel, Leslie J and Reiner, Alex P and Kenneth Rice and Robinson, Jennifer G and Rosendaal, Frits R and Schmidt, Carsten Oliver and Schreiner, Pamela J and Schwettmann, Lars and Shikany, James M and Shu, Xiao-Ou and Stephen Sidney and Sims, Mario and Smith, Jennifer A and Sotoodehnia, Nona and Strauch, Konstantin and Tai, E Shyong and Taylor, Kent and Andr{\'e} G Uitterlinden and Cornelia M van Duijn and Waldenberger, Melanie and Wee, Hwee-Lin and Wei, Wen-Bin and Wilson, Gregory and Xuan, Deng and Yao, Jie and Zeng, Donglin and Zhao, Wei and Zhu, Xiaofeng and Alan B Zonderman and Becker, Diane M and Ian J Deary and Gieger, Christian and Lakka, Timo A and Lehtim{\"a}ki, Terho and Kari E North and Oldehinkel, Albertine J and Brenda W J H Penninx and Snieder, Harold and Wang, Ya-Xing and David R Weir and Zheng, Wei and Michele K Evans and Gauderman, W James and Gudnason, Vilmundur and Horta, Bernardo L and Liu, Ching-Ti and Dennis O Mook-Kanamori and Alanna C Morrison and Pereira, Alexandre C and Psaty, Bruce M and Amin, Najaf and Fox, Ervin R and Charles Kooperberg and Sim, Xueling and Laura Bierut and Rotter, Jerome I and Sharon L R Kardia and Franceschini, Nora and Rao, Dabeeru C and Myriam Fornage} } @article {12124, title = {Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.}, journal = {Molecular Psychiatry}, volume = {25}, year = {2020}, pages = {2392-2409}, abstract = {

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to~346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 {\texttimes} 10 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 {\texttimes} 10) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 {\texttimes} 10) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

}, keywords = {Biological Specimen Banks, Databases, Factual, Europe, Exome, Female, Genetic Loci, Humans, Male, Polymorphism, Single Nucleotide, Smoking, United Kingdom}, issn = {1476-5578}, doi = {10.1038/s41380-018-0313-0}, author = {Erzurumluoglu, A Mesut and Liu, Mengzhen and Jackson, Victoria E and Barnes, Daniel R and Datta, Gargi and Melbourne, Carl A and Young, Robin and Batini, Chiara and Surendran, Praveen and Jiang, Tao and Adnan, Sheikh Daud and Afaq, Saima and Agrawal, Arpana and Altmaier, Elisabeth and Antoniou, Antonis C and Asselbergs, Folkert W and Baumbach, Clemens and Laura Bierut and Bertelsen, Sarah and Boehnke, Michael and Bots, Michiel L and Brazel, David M and Chambers, John C and Chang-Claude, Jenny and Chen, Chu and Corley, Janie and Chou, Yi-Ling and David, Sean P and de Boer, Rudolf A and Christiaan de Leeuw and Joe G Dennis and Dominiczak, Anna F and Dunning, Alison M and Easton, Douglas F and Charles B Eaton and Elliott, Paul and Evangelou, Evangelos and Jessica Faul and Tatiana Foroud and Goate, Alison and Gong, Jian and Hans-J{\"o}rgen Grabe and Jeffrey Haessler and Christopher A Haiman and Hallmans, G{\"o}ran and Anke R Hammerschlag and Sarah E Harris and Andrew T Hattersley and Andrew C Heath and Hsu, Chris and Iacono, William G and Kanoni, Stavroula and Kapoor, Manav and Kaprio, Jaakko and Sharon L R Kardia and Karpe, Fredrik and Kontto, Jukka and Kooner, Jaspal S and Charles Kooperberg and Kuulasmaa, Kari and Laakso, Markku and Lai, Dongbing and Langenberg, Claudia and Le, Nhung and Lettre, Guillaume and Loukola, Anu and Luan, Jian{\textquoteright}an and Pamela A F Madden and Mangino, Massimo and Riccardo E Marioni and Marouli, Eirini and Marten, Jonathan and Nicholas G Martin and McGue, Matt and Michailidou, Kyriaki and Mihailov, Evelin and Moayyeri, Alireza and Moitry, Marie and M{\"u}ller-Nurasyid, Martina and Naheed, Aliya and Nauck, Matthias and Neville, Matthew J and Sune Fallgaard Nielsen and Kari E North and Markus Perola and Pharoah, Paul D P and Pistis, Giorgio and Tinca J Polderman and Posthuma, Danielle and Neil Poulter and Qaiser, Beenish and Rasheed, Asif and Reiner, Alex and Renstrom, Frida and Rice, John and Rohde, Rebecca and Rolandsson, Olov and Nilesh J Samani and Samuel, Maria and Schlessinger, David and H Steven Scholte and Scott, Robert A and Peter Sever and Shao, Yaming and Shrine, Nick and Smith, Jennifer A and John M Starr and Kathleen E Stirrups and Stram, Danielle and Heather M Stringham and Tachmazidou, Ioanna and Tardif, Jean-Claude and Thompson, Deborah J and Hilary A Tindle and Tragante, Vinicius and Trompet, Stella and Turcot, Val{\'e}rie and Tyrrell, Jessica and Vaartjes, Ilonca and Van Der Leij, Andries R and van der Meer, Peter and Varga, Tibor V and Verweij, Niek and V{\"o}lzke, Henry and Wareham, Nicholas J and Warren, Helen R and David R Weir and Weiss, Stefan and Wetherill, Leah and Yaghootkar, Hanieh and Yavas, Ersin and Jiang, Yu and Chen, Fang and Zhan, Xiaowei and Zhang, Weihua and Zhao, Wei and Zhao, Wei and Zhou, Kaixin and Amouyel, Philippe and Blankenberg, Stefan and Caulfield, Mark J and Chowdhury, Rajiv and Francesco Cucca and Ian J Deary and Deloukas, Panos and Di Angelantonio, Emanuele and Marco M Ferrario and Ferri{\`e}res, Jean and Franks, Paul W and Timothy M Frayling and Frossard, Philippe and Hall, Ian P and Caroline Hayward and Jansson, Jan-H{\r a}kan and Jukema, J Wouter and Kee, Frank and M{\"a}nnist{\"o}, Satu and Andres Metspalu and Munroe, Patricia B and B{\o}rge G Nordestgaard and Palmer, Colin N A and Veikko Salomaa and Sattar, Naveed and Timothy Spector and David P Strachan and van der Harst, Pim and Zeggini, Eleftheria and Saleheen, Danish and Adam S Butterworth and Wain, Louise V and Gon{\c c}alo R Abecasis and Danesh, John and Tobin, Martin D and Scott Vrieze and Liu, Dajiang J and Howson, Joanna M M} } @article {10225, title = {A meta-analysis of genome-wide association studies identifies multiple longevity genes.}, journal = {Nature Communications}, volume = {10}, year = {2019}, month = {08/2019}, pages = {3669}, abstract = {

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

}, keywords = {genes, Genome-Wide Association Study, GWA, longevity genes, meta-analysis}, issn = {2041-1723}, doi = {10.1038/s41467-019-11558-2}, url = {https://www.ncbi.nlm.nih.gov/pubmed/31413261}, author = {Deelen, Joris and Daniel S Evans and Dan E Arking and Tesi, Niccol{\`o} and Nygaard, Marianne and Liu, Xiaomin and Wojczynski, Mary K and Biggs, Mary L and van der Spek, Ashley and Atzmon, Gil and Erin B Ware and Sarnowski, Chlo{\'e} and Albert Vernon Smith and Sepp{\"a}l{\"a}, Ilkka and Cordell, Heather J and Dose, Janina and Amin, Najaf and Alice M. Arnold and Kristin L. Ayers and Barzilai, Nir and Becker, Elizabeth J and Beekman, Marian and Blanch{\'e}, H{\'e}l{\`e}ne and Christensen, Kaare and Christiansen, Lene and Collerton, Joanna C and Cubaynes, Sarah and Steven R Cummings and Davies, Karen and Debrabant, Birgit and Deleuze, Jean-Fran{\c c}ois and Duncan, Rachel and Jessica Faul and Franceschi, Claudio and Galan, Pilar and Gudnason, Vilmundur and Tamara B Harris and Huisman, Martijn and Hurme, Mikko A and Jagger, Carol and Jansen, Iris and Jylh{\"a}, Marja and K{\"a}h{\"o}nen, Mika and Karasik, David and Sharon L R Kardia and Kingston, Andrew and Kirkwood, Thomas B L and Lenore J Launer and Lehtim{\"a}ki, Terho and Lieb, Wolfgang and Lyytik{\"a}inen, Leo-Pekka and Martin-Ruiz, Carmen and Min, Junxia and Nebel, Almut and Anne B Newman and Nie, Chao and Nohr, Ellen A and Orwoll, Eric S and Thomas T Perls and Province, Michael A and Psaty, Bruce M and Olli T Raitakari and Reinders, Marcel J T and Robine, Jean-Marie and Rotter, Jerome I and Sebastiani, Paola and Jennifer A Smith and S{\o}rensen, Thorkild I A and Kent D Taylor and Andr{\'e} G Uitterlinden and van der Flier, Wiesje and Sven J van der Lee and Cornelia M van Duijn and van Heemst, Diana and James W Vaupel and David R Weir and Ye, Kenny and Zeng, Yi and Zheng, Wanlin and Holstege, Henne and Douglas P Kiel and Kathryn L Lunetta and Eline P Slagboom and Joanne M Murabito} } @article {12128, title = {Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.}, journal = {Nature Communications}, volume = {10}, year = {2019}, pages = {376}, abstract = {

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Asians, Blacks, Brazil, Calcium-Binding Proteins, Cholesterol, Cholesterol, HDL, Cholesterol, LDL, Exercise, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Hispanic or Latino, Humans, LIM-Homeodomain Proteins, Lipid Metabolism, Lipids, Male, Membrane Proteins, Microtubule-Associated Proteins, Middle Aged, Muscle Proteins, Nerve Tissue Proteins, Transcription Factors, Triglycerides, Whites, Young Adult}, issn = {2041-1723}, doi = {10.1038/s41467-018-08008-w}, author = {Kilpel{\"a}inen, Tuomas O and Bentley, Amy R and Noordam, Raymond and Yun Ju Sung and Schwander, Karen and Thomas W Winkler and Jakupovi{\'c}, Hermina and Daniel I Chasman and Alisa Manning and Ntalla, Ioanna and Aschard, Hugues and Brown, Michael R and de Las Fuentes, Lisa and Franceschini, Nora and Guo, Xiuqing and Vojinovic, Dina and Aslibekyan, Stella and Feitosa, Mary F and Kho, Minjung and Musani, Solomon K and Melissa Richard and Wang, Heming and Wang, Zhe and Traci M Bartz and Bielak, Lawrence F and Campbell, Archie and Dorajoo, Rajkumar and Fisher, Virginia and Hartwig, Fernando P and Horimoto, Andrea R V R and Li, Changwei and Kurt Lohman and Marten, Jonathan and Sim, Xueling and Smith, Albert V and Tajuddin, Salman M and Alver, Maris and Amini, Marzyeh and Boissel, Mathilde and Jin-Fang Chai and Chen, Xu and Divers, Jasmin and Evangelou, Evangelos and Gao, Chuan and Graff, Mariaelisa and Sarah E Harris and He, Meian and Hsu, Fang-Chi and Jackson, Anne U and Jing Hua Zhao and Kraja, Aldi T and K{\"u}hnel, Brigitte and Laguzzi, Federica and Lyytik{\"a}inen, Leo-Pekka and Ilja M Nolte and Rauramaa, Rainer and Riaz, Muhammad and Robino, Antonietta and Rueedi, Rico and Heather M Stringham and Takeuchi, Fumihiko and van der Most, Peter J and Varga, Tibor V and Verweij, Niek and Erin B Ware and Wen, Wanqing and Li, Xiaoyin and Yanek, Lisa R and Amin, Najaf and Donna K Arnett and Boerwinkle, Eric and Brumat, Marco and Brian E Cade and Canouil, Micka{\"e}l and Chen, Yii-Der Ida and Concas, Maria Pina and Connell, John and de Mutsert, Ren{\'e}e and de Silva, H Janaka and de Vries, Paul S and Demirkan, Ayse and Ding, Jingzhong and Charles B Eaton and Jessica Faul and Friedlander, Yechiel and Gabriel, Kelley P and Ghanbari, Mohsen and Giulianini, Franco and Gu, Chi Charles and Gu, Dongfeng and Tamara B Harris and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hunt, Steven C and Ikram, M Arfan and Jost Bruno Jonas and Koh, Woon-Puay and Komulainen, Pirjo and Krieger, Jose E and Stephen B Kritchevsky and Kutalik, Zolt{\'a}n and Kuusisto, Johanna and Langefeld, Carl D and Langenberg, Claudia and Lenore J Launer and Leander, Karin and Lemaitre, Rozenn N and Lewis, Cora E and Liang, Jingjing and Liu, Jianjun and M{\"a}gi, Reedik and Manichaikul, Ani and Meitinger, Thomas and Andres Metspalu and Milaneschi, Yuri and Mohlke, Karen L and Thomas H Mosley and Murray, Alison D and Michael A Nalls and Nang, Ei-Ei Khaing and Nelson, Christopher P and Nona, Sotoodehnia and Norris, Jill M and Nwuba, Chiamaka Vivian and Jeff O{\textquoteright}Connell and Palmer, Nicholette D and Papanicolau, George J and Pazoki, Raha and Nancy L Pedersen and Peters, Annette and Peyser, Patricia A and Polasek, Ozren and David J Porteous and Poveda, Alaitz and Olli T Raitakari and Rich, Stephen S and Neil Risch and Robinson, Jennifer G and Rose, Lynda M and Rudan, Igor and Schreiner, Pamela J and Scott, Robert A and Stephen Sidney and Sims, Mario and Smith, Jennifer A and Snieder, Harold and Sofer, Tamar and John M Starr and Sternfeld, Barbara and Strauch, Konstantin and Tang, Hua and Kent D Taylor and Tsai, Michael Y and Tuomilehto, Jaakko and Andr{\'e} G Uitterlinden and van der Ende, M Yldau and van Heemst, Diana and Voortman, Trudy and Waldenberger, Melanie and Wennberg, Patrik and Wilson, Gregory and Xiang, Yong-Bing and Yao, Jie and Yu, Caizheng and Yuan, Jian-Min and Zhao, Wei and Alan B Zonderman and Becker, Diane M and Boehnke, Michael and Bowden, Donald W and de Faire, Ulf and Ian J Deary and Elliott, Paul and T{\~o}nu Esko and Freedman, Barry I and Froguel, Philippe and Paolo P. Gasparini and Gieger, Christian and Kato, Norihiro and Laakso, Markku and Lakka, Timo A and Lehtim{\"a}ki, Terho and Patrik K E Magnusson and Oldehinkel, Albertine J and Brenda W J H Penninx and Nilesh J Samani and Shu, Xiao-Ou and van der Harst, Pim and Jana V. van Vliet-Ostaptchouk and Vollenweider, Peter and Wagenknecht, Lynne E and Wang, Ya X and Wareham, Nicholas J and David R Weir and Wu, Tangchun and Zheng, Wei and Zhu, Xiaofeng and Michele K Evans and Franks, Paul W and Gudnason, Vilmundur and Caroline Hayward and Horta, Bernardo L and Tanika N Kelly and Liu, Yongmei and Kari E North and Pereira, Alexandre C and Ridker, Paul M and Tai, E Shyong and van Dam, Rob M and Fox, Ervin R and Sharon L R Kardia and Liu, Ching-Ti and Dennis O Mook-Kanamori and Province, Michael A and Redline, Susan and Cornelia M van Duijn and Rotter, Jerome I and Charles Kooperberg and Gauderman, W James and Psaty, Bruce M and Kenneth Rice and Munroe, Patricia B and Myriam Fornage and Cupples, L Adrienne and Charles N Rotimi and Alanna C Morrison and Rao, Dabeeru C and Ruth J F Loos} } @article {9049, title = {Mortality selection in a genetic sample and implications for association studies.}, journal = {International Journal of Epidemiolpgy}, volume = {46}, year = {2017}, month = {08/2017}, abstract = {

Background: Mortality selection occurs when a non-random subset of a population of interest has died before data collection and is unobserved in the data. Mortality selection is of general concern in the social and health sciences, but has received little attention in genetic epidemiology. We tested the hypothesis that mortality selection may bias genetic association estimates, using data from the US-based Health and Retirement Study (HRS).

Methods: We tested mortality selection into the HRS genetic database by comparing HRS respondents who survive until genetic data collection in 2006 with those who do not. We next modelled mortality selection on demographic, health and social characteristics to calculate mortality selection probability weights. We analysed polygenic score associations with several traits before and after applying inverse-probability weighting to account for mortality selection. We tested simple associations and time-varying genetic associations (i.e. gene-by-cohort interactions).

Results: We observed mortality selection into the HRS genetic database on demographic, health and social characteristics. Correction for mortality selection using inverse probability weighting methods did not change simple association estimates. However, using these methods did change estimates of gene-by-cohort interaction effects. Correction for mortality selection changed gene-by-cohort interaction estimates in the opposite direction from increased mortality selection based on analysis of HRS respondents surviving through 2012.

Conclusions: Mortality selection may bias estimates of gene-by-cohort interaction effects. Analyses of HRS data can adjust for mortality selection associated with observables by including probability weights. Mortality selection is a potential confounder of genetic association studies, but the magnitude of confounding varies by trait.

}, keywords = {Genetics, GWAS, Mortality}, issn = {1464-3685}, doi = {10.1093/ije/dyx041}, author = {Benjamin W Domingue and Daniel W. Belsky and Harrati, Amal and Dalton C Conley and David R Weir and Jason D Boardman} } @article {8885, title = {Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.}, journal = {Nat Genet}, volume = {48}, year = {2016}, month = {2016 Oct}, pages = {1162-70}, abstract = {

Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.

}, issn = {1546-1718}, doi = {10.1038/ng.3660}, author = {Liu, Chunyu and Kraja, Aldi T and Jennifer A Smith and Brody, Jennifer A and Franceschini, Nora and Joshua C. Bis and Kenneth Rice and Alanna C Morrison and Lu, Yingchang and Weiss, Stefan and Guo, Xiuqing and Walter R Palmas and Martin, Lisa W and Yii-Der I Chen and Surendran, Praveen and Drenos, Fotios and Cook, James P and Auer, Paul L and Chu, Audrey Y and Giri, Ayush and Wei Zhao and Jakobsdottir, Johanna and Lin, Li-An and Stafford, Jeanette M and Amin, Najaf and Mei, Hao and Yao, Jie and Voorman, Arend and Larson, Martin G and Grove, Megan L and Albert Vernon Smith and Hwang, Shih-Jen and Chen, Han and Huan, Tianxiao and Kosova, Gulum and Stitziel, Nathan O and Kathiresan, Sekar and Nilesh J Samani and Schunkert, Heribert and Deloukas, Panos and Li, Man and Fuchsberger, Christian and Pattaro, Cristian and Gorski, Mathias and Charles Kooperberg and George J Papanicolaou and Rossouw, Jacques E and Jessica Faul and Sharon L R Kardia and Bouchard, Claude and Raffel, Leslie J and Andr{\'e} G Uitterlinden and Franco, Oscar H and Ramachandran S Vasan and O{\textquoteright}Donnell, Christopher J and Kent D Taylor and Liu, Kiang and Erwin P Bottinger and Gottesman, Omri and Daw, E Warwick and Giulianini, Franco and Ganesh, Santhi and Salfati, Elias and Tamara B Harris and Lenore J Launer and D{\"o}rr, Marcus and Felix, Stephan B and Rettig, Rainer and V{\"o}lzke, Henry and Eric S Kim and Lee, Wen-Jane and Lee, I-Te and Sheu, Wayne H-H and Tsosie, Krystal S and Digna R Velez Edwards and Yongmei Liu and Correa, Adolfo and David R Weir and V{\"o}lker, Uwe and Ridker, Paul M and Boerwinkle, Eric and Gudnason, Vilmundur and Reiner, Alexander P and Cornelia M van Duijn and Ingrid B Borecki and Edwards, Todd L and Chakravarti, Aravinda and Rotter, Jerome I and Psaty, Bruce M and Ruth J F Loos and Myriam Fornage and Georg B Ehret and Newton-Cheh, Christopher and Levy, Daniel and Daniel I Chasman} } @article {7168, title = {Mechanisms for racial and ethnic disparities in glycemic control in middle-aged and older Americans in the health and retirement study.}, journal = {Arch Intern Med}, volume = {167}, year = {2007}, month = {2007 Sep 24}, pages = {1853-60}, publisher = {167}, abstract = {

BACKGROUND: Mechanisms for racial/ethnic disparities in glycemic control are poorly understood.

METHODS: A nationally representative sample of 1901 respondents 55 years or older with diabetes mellitus completed a mailed survey in 2003; 1233 respondents completed valid at-home hemoglobin A(1c) (HbA(1c)) kits. We constructed multivariate regression models with survey weights to examine racial/ethnic differences in HbA(1c) control and to explore the association of HbA(1c) level with sociodemographic and clinical factors, access to and quality of diabetes health care, and self-management behaviors and attitudes.

RESULTS: There were no significant racial/ethnic differences in HbA(1c) levels in respondents not taking antihyperglycemic medications. In 1034 respondents taking medications, the mean HbA(1c) value (expressed as percentage of total hemoglobin) was 8.07\% in black respondents and 8.14\% in Latino respondents compared with 7.22\% in white respondents (P < .001). Black respondents had worse medication adherence than white respondents, and Latino respondents had more diabetes-specific emotional distress (P < .001). Adjusting for hypothesized mechanisms accounted for 14.0\% of the higher HbA(1c) levels in black respondents and 19.0\% in Latinos, with the full model explaining 22.0\% of the variance. Besides black and Latino ethnicity, only insulin use (P < .001), age younger than 65 years (P = .007), longer diabetes duration (P = .004), and lower self-reported medication adherence (P = .04) were independently associated with higher HbA(1c) levels.

CONCLUSIONS: Latino and African American respondents had worse glycemic control than white respondents. Socioeconomic, clinical, health care, and self-management measures explained approximately a fifth of the HbA(1c) differences. One potentially modifiable factor for which there were racial disparities--medication adherence--was among the most significant independent predictors of glycemic control.

}, keywords = {Aged, Aged, 80 and over, Black People, Diabetes Mellitus, Female, Glycated Hemoglobin, Health Services Accessibility, Hispanic or Latino, Humans, Longitudinal Studies, Male, Middle Aged, Patient Compliance, Socioeconomic factors, Treatment Refusal, United States, White People}, issn = {0003-9926}, doi = {10.1001/archinte.167.17.1853}, author = {Michele M Heisler and Jessica Faul and Rodney A. Hayward and Kenneth M. Langa and Caroline S Blaum and David R Weir} }